1H MRSI/Response Inhibition/Methamphetamine Abusers

描述（由申请人提供）：项目摘要：符合NIDA的使命，利用科学来了解药物滥用和成瘾，这个建议服务于长期目标的本地化和表征慢性甲基苯丙胺滥用，一个广泛的条件，主要的公共卫生重要性的结构和功能的神经病理学。该项目的重点是甲基安非他明滥用中反应抑制能力的减弱。受损的反应抑制可能是额纹状体功能障碍的表现，并被认为是延续成瘾和损害治疗结果。具体来说，这个项目将调查与反应抑制有关的大脑区域的代谢和/或受甲基苯丙胺滥用的影响。将使用质子磁共振波谱成像（1H MRSI）分析神经代谢，这是一种在这种情况下使用相对较少的技术。甲基苯丙胺滥用者将在短暂戒断后进入治疗前接受非侵入性体内1H MRSI扫描，并将其与年龄和性别匹配的健康对照组进行比较。研究终点将包括下额叶皮质、前扣带皮质、前扣带白色物质和丘脑核中代谢物N-乙酰化合物、谷氨酸、+谷氨酰胺+ GABA、肌酸+磷酸肌酸、胆碱化合物和肌醇的水平。我们将获得1H MRSI在射击回波时间允许我们采样更多的神经代谢物从更多的大脑结构在更高的空间分辨率比以前的研究报告。这提高了检测任何代谢物异常的可能性，这些代谢物异常可能与甲基苯丙胺滥用有关，并允许它们在大脑结构和组织类型方面更精确地定位。因此，我们将在进入治疗时捕获甲基苯丙胺成瘾者大脑的广泛代谢概况。本案无关滥用非法甲基苯丙胺在美国和国外是一个严重的流行病比例的公共卫生问题。对许多人来说，甲基苯丙胺成瘾如此难以克服的一个可能原因是成瘾者抑制自己寻求药物的能力被认为受到脑损伤的影响。该项目将研究被认为负责甲基苯丙胺成瘾者的甲基苯丙胺抑制和/或损伤的大脑部分的化学物质。

DESCRIPTION (provided by applicant): Project Summary: Consistent with the NIDA mission of using science to understand drug abuse and addiction, this proposal serves the long-term objective of localizing and characterizing structural and functional neuropathology in chronic methamphetamine abuse, a widespread condition of major public health importance. The project focuses on diminished capacity for response inhibition in methamphetamine abuse. Impaired response inhibition is a likely manifestation of frontostriatal dysfunction and is believed to perpetuate addiction and to compromise treatment outcome. Specifically, this project will investigate the metabolism of brain regions involved with response inhibition and/or afflicted by methamphetamine abuse. Neurometabolism will be assayed with proton magnetic resonance spectroscopic imaging (1H MRSI), a comparatively underused technology in this condition. Methamphetamine abusers will undergo non-invasive, in vivo 1H MRSI scans just before entering treatment after brief abstinence and will be compared to age- and sex-matched healthy controls. Study endpoints will include levels of the metabolites A/-acetyl compounds, glutamate;+ glutamine + GABA, creatine +'phosphocreatine, choline compounds, and myo-inositol in inferior frontal cortex, anterior cingulate cortex, anterior cingulate white matter, and nucleus accumbens. We will acquire 1H MRSI at shot echo-time permitting us to sample a greater number of neurometabolites from more brain strucures at higher spatial resolution than reported in previous studies. This raises the probability of detecting any metabolite abnormalities that mayattend methamphetamine abuse and allows them to be localized with greater precision in terms of brain structure and tissue type. We will thus capture a wide metabolic profile of the methamphetamine addict's brain at time of entry into treatment. Relevance. Abuse of illicit methamphetamines is a serious public health problem of epidemic proportion in the US and abroad. One (1) possible reason methampetamine addiction is so difficult for many to overcome is that the addict's ability to inhibit him-or herself in seeking drug is thought to be compromised by brain damage. This project will examine the chemistry of parts of the brain thought to be responsible for inhibition and/or damaged by methamphetamine in methamphetamine addicts.